The present invention relates generally to cytokine receptors, and more specifically, to Interleukin-7 receptors.
Interleukin-7 (IL-7, also known as pre-B cell growth factor and lymphopoietin-1) is a mammalian endogenous secretory protein which is capable of inducing proliferation of bone marrow-derived lymphocyte progenitors and precursors, including the specialized precursors .known as pre-B cells. IL-7 is also believed to be capable of stimulating other cell types, such as T cells and megakaryocytes; however, the full repertoire of cells capable of responding to IL-7 is not yet known. It is likely that IL-7 acts on a variety of cell types. Complementary DNA clones encoding IL-7 have recently been isolated (Goodwin et al., Proc. Natl. Acad. Sci. USA 86:302, 1989; Namen et al., Nature 333:571, 1988), permitting further structural and biological characterization of IL-7.
IL-7 initiates its biological effect on cells by binding to a specific 1L-7 receptor protein expressed on the plasma membrane of an IL-7-responsive cell. Because of the ability of IL-7 to specifically bind IL-7 receptor (IL-7R), purified IL-7R compositions will be useful in diagnostic assays for IL-7, as well as in raising antibodies to IL-7 receptor for use in diagnosis and therapy. In addition, purified IL-7 receptor compositions may be used directly in therapy to bind or scavenge IL-7, thereby providing a means for regulating the immune activities of this cytokine. In order to study the structural and biological characteristics of IL-7R and the role played by IL-7R in the responses of various cell populations to IL-7 or other cytokine stimulation, or to use IL-7R effectively in therapy, diagnosis, or assay, purified compositions of IL-7R are needed. Such compositions, however, are obtainable in practical yields only by cloning and expressing genes encoding the receptors using recombinant DNA technology. Efforts to purify the IL-7R molecule for use in biochemical analysis or to clone and express mammalian genes encoding IL-7R have been impeded by lack of a suitable source of receptor protein or mRNA. Prior to the present invention, no cell lines were known to express high levels of IL-7R constitutively and continuously, which precluded purification of receptor for sequencing or construction of genetic libraries for direct expression cloning.